Antimicrobials and Antimicrobial Resistance

Question 1

what is virulence

Answer 1

how pathogenic an organism is

Question 2

what are antibiotics

Answer 2

limit the growth of microorganisms

Question 3

first modern antibiotics were

Answer 3

synthetic

Question 4

treatment of syphilis

Answer 4

ehrlich screen arsenic-containing compounds

Question 5

bacteria that creates syphilis

Answer 5

Treponema pallidum

Question 6

synthetic antibiotics in use today

Answer 6

sulfa drugs, quinolines, oxazolidinones

Question 7

who came up with the first modern antibiotics

Answer 7

paul ehrlich

Question 8

who discovered the first natural antibiotic and how

Answer 8

alexander fleming
observed an area of no bacterial growth on a plate surrounding some mould

Question 9

when was the first patient treatment

Answer 9

1942

Question 10

howard florey and ernst chain developed

Answer 10

penicillin production on industrial scales

Question 11

hodgkin discovered

Answer 11

structure of penicillin

Question 12

what did the discovery of structure of penicillin allow for

Answer 12

-rational chemical modification
-semi-synthetic antibiotics
-promote stability, reduce toxicity, enhance potency

Question 13

what is a major source of antibiotics

Answer 13

streptomyces

Question 14

streptomyces

Answer 14

soil bacteria: gram-positive, filamentous bacillus, aerobic and spore-forming
elaborate secondary metabolism
looks more like a fungi than a bacteria
produce geosmin: smell of rain
produce 2/3 of clinical useful antibiotics ending in -mycin

Question 15

antibiotics are often

Answer 15

secondary metabolites

Question 16

what is not required for homeostasis

Answer 16

secondary metabolism

Question 17

secondary metabolites are produced during

Answer 17

stationary phase

Question 18

secondary metabolites can have

Answer 18

unusual, complex chemical structures

Question 19

bactericidal

Answer 19

kill bacteria

Question 20

bacteriostatic

Answer 20

prevent the growth of bacteria

Question 21

no new class of antibiotics have been developed in

Answer 21

15-20 years

Question 22

antibiotic development is

Answer 22

slow and expensive

Question 23

crowded plate technique

Answer 23

plate dilute solution of soil bacteria on a plate and look for zones of inhibition

Question 24

effective antibiotics should selectively target

Answer 24

bacterial structures/metabolism but not mammalian

Question 25

antibiotic effectiveness depends on

Answer 25

physiology of target bacteria

Question 26

targets of antibiotics - gram positive cell wall synthesis

Answer 26

requires crosslinking of peptidoglycan for cell wall integrity penicillin blocks insertion of interpeptide pentapeptide penicillin resembles peptidoglycan subunit and binds penicillin-binding protein (transpeptidase) this blocks the crosslinking enzyme and the cell wall cannot rebuild and it dies

Question 27

targets of antibiotics - bacterial cell membrane

Answer 27

polymyxin binds to LPS disrupts outer and inner membrane of gram-negative bacteria leads to cell lysis

Question 28

targets of antibiotics - bacterial ribosomes

Answer 28

major classes of protein synthesis-inhibiting antibacterials: chloramphenical, macrolides, lincosamides bind to large subunit and stops protein synthesis aminoglycosides bind to small subunit and impairs proofreading, produces faulty proteins tetracyclines bind to small subunit and blocks the binding of tRNAs to inhibit protein synthesis

Question 29

targets of antibiotics - nucleic acid synthesis

Answer 29

requires topoisomerases and gyrase to prevent supercoiling quinolones inhibit the activity of DNA gyrase domains, causing supercoiling

Question 30

targets of antibiotics - metabolic pathways

Answer 30

blocks folic acid synthesis which is required for nucleotide synthesis sulfonamide and trimethoprim are both antimetabolites competitive inhibitors

Question 31

folic acid is _______ in bacteria, but is obtained through ____ in humans

Answer 31

synthesized diet

Question 32

minimum inhibitory concentration

Answer 32

lowest does that inhibits bacteria growth

Question 33

minimum bactericidal concentration

Answer 33

lowest dose that kills bacteria

Question 34

MIC and MBC is important to

Answer 34

maintain an effective concentration of antibiotics in the body

Question 35

antibiotic resistance

Answer 35

efflux pump blocked penetration inactivation by enzymes target modification

Question 36

antibiotic resistance - efflux pumps

Answer 36

solute pumps, requires ATP removes amphipathic molecules from cytoplasm (bile salts) broad substrate specificity

Question 37

antibiotic resistance - beta-lactamases

Answer 37

an enzyme that cleaves beta-lactam rings ring present in penicillin-derived drugs cleavage prevents proper targeting of drug

Question 38

acquiring antibiotic resistance genes

Answer 38

acquired vertically and horizontally can be acquired by transformation, transduction or conjugation core genomes of bacteria acquire mutations over time which can limit susceptibility to antibiotics mutations quickly become fixed if there is no fitness cost or a benefit

Question 39

what is the fastest and most common means of spreading resistance

Answer 39

conjugation of plasmids inter- and intraspecies

Question 40

ESKAPE pathogens

Answer 40

important targets for antibiotic development common causes of nosocomial infections found to be multidrug-resistant

Question 41

multidrug-resistant bacteria

Answer 41

are resistant to more than three classes of antibiotics

Question 42

biofilms limit

Answer 42

penetration of antibiotics and promote the spread of antibiotic resistance genes

Question 43

phage therapy

Answer 43

lytic phage kill bacteria during egress difficult to match a phage with a particular strain of bacteria (must be permissive)

Question 44

antivirals

Answer 44

drugs target viral proteins during all phases of the replication cycle

Question 45

how do viruses change the cells

Answer 45

reprogram host cell metabolism use cellular proteins for non-typical purposes

Question 46

antivirals - nucleic acid synthesis

Answer 46

works as chain-terminators prevent new DNA chains from being formed

Question 47

chain-terminators

Answer 47

halt extension from 5' to 3' on new strand by lack of 3' hydroxyl group

Question 48

antivirals- targeting proteases

Answer 48

act on both viral and host proteins inhibitors resemble normal protease target, but lack cleavage site prevents viruses from making copies of itself

Question 49

resistance to antivirals

Answer 49

high mutation rate generate a large amount of progeny virions co-infection of cells with multiple viruses is common viral genomes can complement defects in co-infecting genomes inhibited viruses are quickly selected against, leaving more host cells for resistant viruses

Question 50

resistance to antivirals: serine to aspargine

Answer 50

M2 ion channel is present in the influenza A virus envelope allows protons to enter the virion to releease genome segments from M1 matrix protein amantadine blocks the M2 ion channel inhibiting viral uncoating a single AA change in the channel is sufficient to prevent Amantadine binding without loss of conductivity mutation and resistance is now widespread

Question 51

combination therapy - HIV

Answer 51

HIV has an extremely high mutation rate diversity from both viral polymerase and cystine deamination by host innate immune factor APOBEC3 anti-retrovirals target viral proteins used in combinations or three or four to limit emergence of resistance same strategy used to cure Hepatitis C virus

Question 52

targeting host proteins to limit SARS-CoV-2 replication

Answer 52

treat with increasing concentration of TMPRSS2 inhibitor, Camostat reduces infection camostat prevented viral entry camostat already approved for clinical use difficult for viruses to evolve away from dependence on host targets